Abstract
Noncanonical nucleic acid structures, such as G-quadruplex (G4) and i-Motif (iM), have attracted increasing research interests because of their unique structural and binding properties, as ...well as their important biological activities. To date, thousands of small molecules that bind to varying G4/iM structures have been designed, synthesized and tested for diverse chemical and biological uses. Because of the huge potential and increasing research interests on G4-targeting ligands, we launched the first G4 ligand database G4LDB in 2013. Here, we report a new version, termed G4LDB 2.2 (http://www.g4ldb.com), with upgrades in both content and function. Currently, G4LDB2.2 contains >3200 G4/iM ligands, ∼28 500 activity entries and 79 G4–ligand docking models. In addition to G4 ligand library, we have also added a brand new iM ligand library to G4LDB 2.2, providing a comprehensive view of quadruplex nucleic acids. To further enhance user experience, we have also redesigned the user interface and optimized the database structure and retrieval mechanism. With these improvements, we anticipate that G4LDB 2.2 will serve as a comprehensive resource and useful research toolkit for researchers across wide scientific communities and accelerate discovering and validating better binders and drug candidates.
Mn/TiO2 catalysts were synthesized using a deposition–precipitation method. Ru-doped Mn/TiO2 catalysts were prepared by an incipient-wetness impregnation method. To investigate the interaction ...between Ru and Mn species, the catalytic performance of Mn/TiO2 and Ru–Mn/TiO2 catalysts in the catalytic oxidation of chlorobenzene (CB) was evaluated. The physicochemical properties of the catalysts were characterized by XRD, HRTEM, XPS, EPR, H2-TPR, O2-TPD and so on. The results showed that the 0.8% Ru-10% Mn/TiO2 catalyst exhibited the best catalytic activity with 99% CB conversion at 250 °C and showed an excellent CO2 yield (95% at 300 °C) and stability. In comparison with the 10% Mn/TiO2 catalyst, the T90 of the Ru–Mn/TiO2 catalyst decreased by 60 °C, which was attributed to the interaction between Ru and Mn species at the interfaces of Ru/Mn. The Ru species increased the concentration of Mn4+ and Ru4+ and reduced the H2 reduction temperature, which was conducive to improving the redox performance of the catalysts. Ru species were highly dispersed on the Mn/TiO2 catalyst surfaces, forming a large number of Ru/Mn interfaces. The interaction between Ru and Mn species at the interfaces of Ru/Mn promoted the formation of oxygen vacancies and surface reactive oxygen species, thus enhancing the catalytic activity.
Migraine is a complex neurological disorder with a high disability rate. Although the precipitating factors of migraine remain unclear, previous studies suggest that when there is excess nitrogen ...dioxide (NO2) pollution in the atmosphere, the medical demand due to migraine attacks increases sharply. However, the main role of NO2 as a trigger for migraine is not yet well understood. The purpose of this study was to explore the relationship between NO2 exposure and the occurrence of migraine as well as the possible underlying mechanisms. We first investigated whether repeated short-term NO2 exposure could induce behavioural and biological migraine phenotypes in rats. Next, capsazepine (CZP) was used to block transient receptor potential cation channel subfamily V member 1 (TRPV1) in vivo, and CZP and vitamin E (VE) were used to verify the role of reactive oxygen species (ROS)-TRPV1 signalling in NO2-induced migraine in primary trigeminal neurones in vitro. We demonstrated that short-term repeated NO2 exposure can significantly induce migraine in rats, and its key molecular mechanism may be related to ROS burst and its downstream TRPV1 channel activation. The findings of this study will enhance the understanding of the neurotoxic mechanism of NO2, provide new clues for identifying the aetiology of migraine, and lay a new experimental basis for implementing migraine-related preventive and therapeutic control measures.
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•Short-term repeated exposure to ambient NO2 triggered migraine in rats.•NO2-induced migraine in rats was associated with oxidative stress and inflammation.•TRPV1 inhibitor alleviated NO2-induced migraine in rats.•ROS-TRPV1 signalling played a key role in NO2-induced migraine in rats.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The structural, electronic and magnetic properties of Aun+1 and AunNi (n = 1–9) clusters have been investigated using an unbiased CALYPSO structure searching method in conjunction with density ...functional theory. The structural searches show that Ni atom in the lowest energy AunNi cluster favors the most highly coordinated position. The ground state Aun+1 and AunNi clusters possess a planar structure, except for Au6Ni and Au8Ni. Vibrational spectra and photoelectron spectra are predicted to identify their structures in the future. The relative stability and chemical activity are analyzed based on the averaged binding energy, dissociation energy and energy gap for the most stable clusters. It is found that the dopant atom can enhance the thermal stability of the gold clusters. The magic number of stability is 5 for both Aun+1 and AunNi clusters. The substitution of a Ni atom for an Au atom significantly decreases energy gap of Aun clusters with even n. The magnetism calculations show that the magnetic moments of Ni atom in AunNi clusters are reduced by 0.56–2 μB. This reduction may be attributed to the internal charge transfer from 4s to 3d orbital.
•Single Ni atom in Au-Ni alloy clusters tends to occupy the position with the maximum coordination.•The Ni-dopant atom can substantially enhance the thermal stability of the gold clusters.•The change of magnetic moment is proportional to the charge transfer.•The magic Au5Ni clusters could be used as magnetic material with high temperature resistance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Considering the highly carcinogenic and mutagenic of anionic azo dyes to the environment and humans, the development of high efficiency adsorbent for them are of great significance. In this study, a ...novel hydroxyl-riched covalent organic framework (denoted as COF–OH), which can act as an advance adsorbent for anionic azo dyes, was fabricated for the first time. The as-prepared COF–OH demonstrated good dispersion in water, remarkable adsorption performances and good selectivity for anionic azo dyes including eriochrome black T, eriochrome blue black R and congo red. The adsorption capacities of them ranged from 90.71 to 229.12 mg g−1, and the extraction efficiencies of them (>75.91%) were much higher than other dyes (e.g. Methylene blue, direct red 80, 1.46%–39.57%). By optimizing the adsorption conditions (adsorbent dosage, adsorption time, pH, and salt concentration) and desorption conditions (desorption solvent, desorption time and desorption frequency), a dispersive micro solid-phase extraction (D-μ-SPE) method was developed. Further, coupled D-μ-SPE with HPLC-PDA analysis, an effective method was fabricated for the extraction and detection of three selected dyes. The method showed good linearity in the range of 0.1–200 μg mL−1 (R2 > 0.9966), low limits of quantification (0.10 μg mL−1-2.00 μg mL−1), low limits of detection (0.03–1.50 μg mL−1) and good precision. Finally, the COF–OH based D-μ-SPE was successfully applied to extract three selected dyes from water samples (recoveries ranged from 73.90 to 104.00%) and congo red from beverages (recoveries ranged from 81.40 to 111.80%). Besides, by using computer simulation, FT-IR and UV–vis analysis, the adsorption mechanisms of COF–OH to three selected dyes were explored preliminarily.
A novel hydroxyl-riched covalent organic framework (COF–OH) was successfully prepared and applied act as an advanced adsorbent for the D-μ-SPE of anionic azo dyes. Display omitted
•Synthesis of a novel hydroxyl-functionalized covalent organic framework (COF–OH).•COF–OH had good water dispersion and outstanding adsorption performance.•COF–OH showed remarkable performances in the adsorption of three selected anionic azo dyes.•COH–OH based D-μ-SPE can be used to enrich target dyes in water or beverage samples.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Fatty acid synthase (FASN) is generally over-expressed in human tumor tissues and catalyzes de novo synthesis of fatty acids on which tumor cells depend. Bestatin, an inhibitor of ...aminopeptidase/CD13, is one of the dipeptide substrates for the human oligopeptide transporter 1 (PEPT1).
In the current study, we aimed to uncover the role of FASN inhibitors in bestatininduced tumor cell apoptosis and the underlying mechanism, extending our understanding of the correlations between FASN and PEPT1 in cancer and providing a new strategy for tumor targeted treatment.
Cerulenin, orlistat and siRNAs were applied to inhibit FASN. The cell viability and apoptosis were assessed with MTT (thiazolyl blue tetrazolium bromide) assays and annexin VFITC/ PI staining with flow cytometry analysis. Western blot and qRT-PCR analysis were used to detect the protein levels and mRNA levels of the indicated genes in tumor cells, respectively. Protein degradation or stability was examined with cycloheximide chase assays. CD13 activity was detected by gelatin zymography. The HT1080 and C26 xenografts models were conducted to assess the efficacy
.
In the current study, we found that inhibiting FASN by cerulenin and orlistat both augmented the effects of bestatin in decreasing tumor cell viability. Cerulenin increased the apoptosis rates and enhanced the cleavage of PARP caused by bestatin. Furthermore, cerulenin, orlistat and siFASNs markedly elevated PEPT1 protein levels. Indeed, cerulenin induced the upregulation of PEPT1 mRNA expression rather than affecting the protein level after the cells were treated with CHX. And Gly-Sar, a typical competitive substrate of PEPT1, could attenuate the augment of bestatin-induced cell killing by cerulenin. Moreover, synergistic restrain of tumor growth accompanied by a reduction of Ki-67 and increment of TUNEL was significantly achieved in the xenograft models. Interestingly, no clear correlation was observed between the CD13 with FASN and/or PEPT1 in tumor cells.
FASN inhibitors facilitate tumor cells susceptible to bestatin-induced apoptosis involving the up-regulation of PEPT1 at the mRNA translation level and the transport of bestatin by PEPT1, emerging as a promising strategy for tumor targeted therapy.
Zanthoxylum bungeanum Maxim. (Rutaceae) is a known herbal medicine with various bioactivities, including anti-obesity, lipid-lowering, learning & memory improving and anti-diabetes, and amides in Z. ...bungeanum (AZB) are considered as the major active agents for its bioactivities.
This research was carried out to uncover the anti-NAFL effect of AZB and its corresponding molecular mechanisms.
The central composite design-response surface methodology (CCD-RSM) was utilized to optimize the AZB extraction process, and the anti-NAFL effect of AZB was investigated on high fat diet (HFD) fed mice (HFD mice). The levels of ROS in liver tissues were determined using laser confocal microscopy with DCFH-DA probe staining, and anti-enzymes (such as HO-1, SOD, CAT & GSH-PX) and MDA in liver tissues were measured using commercial detecting kits. GC-MS was used to determine the short-chain fatty acids (SCFAs) contents in feces and blood of mice. 16S high-throughput sequencing, western blotting (WB) assay and immunofluorescence (IF) were used to explore the intestinal flora changes in mice and the potential mechanisms of AZB for treatment of NAFL.
Our results showed AZB reduced body weight, alleviated liver pathological changes, reduced fat accumulation, and improved oxidative stress in HFD mice. In addition, we also found AZB improved OGTT and ITT, reduced TG, TC, LDL-C, whereas increased HDL-C in HFD mice. AZB increased total number of the species and interspecies kinship of gut microbiota and reduced the richness and diversity of gut microbiota in HFD mice. Moreover, AZB decreased the ratio of Firmicutes/Bacteroidota, whereas increased the abundance of Allobaculum, Bacteroides and Dubosiella in feces of HFD-fed mice. Furthermore, AZB increased the production of SCFAs, and up-regulated the phosphorylation of AMPK and increased the nuclear transcription of Nrf2 in liver of HFD mice.
Collectively, our results suggested AZB can improve NAFL, which could reduce body weight, reverse liver lesions and fat accumulation, improve oxidative stress in liver tissues of HFD mice. Furthermore, the mechanisms are related to increase of the abundance of high-producing bacteria for SCFAs (e.g. Allobaculum, Bacteroides and Dubosiella) to activate AMPK/Nrf2 signaling.
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•Optimization of extraction process of AZB using RSM.•AZB possesses promising anti- NAFL effects.•AZB regulates the diversity & structure of intestinal microbiota in NAFL mice.•AZB combats NAFL though AMPK/Nrf2 signaling activated by SCFAs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A series of complexes
L2
2
-M
(L2: 6,6″-bis(4-methoxyphenyl)-4′-phenyl-2,2′:6′,2″-terpyridine, M: Mn
2+
, Fe
2+
, Co
2+
, Ni
2+
, Cu
2+
, Zn
2+
) were synthesized by coordinating
p
-methoxyphenyl ...6,6″-substituted terpyridine ligand with first-row transition metal ions and characterized by NMR, ESI-MS, and X-ray single crystal diffraction techniques. Single-crystal structures demonstrated that the steric hindrance of
p
-methoxyphenyl substituents endowed complexes
L2
2
-M
with obvious longer coordination bond lengths and larger bond angles and dihedral angles compared with unmodified
L1
2
-M
(L1: 4′-phenyl-2,2′:6′,2″-terpyridine). The chiral helix geometry was observed for
L2
2
-M
, in which 2,2′:6′,2″-terpyridine moiety dramatically twisted to a spiral form in comparison to the nearly coplanar structure of the parent
L1
2
-M
, resulting in plentiful intramolecular and intermolecular π-π interactions. Also, the appealing racemic (P and M) double helix packed structure for 6,6″-modified bisterpyridine complex
L2
2
-Cu
was formed in the crystal. The consequent appealing charge transfer (CT) emission for
L2
2
-Zn
in the solution and solid were investigated
via
UV-vis and fluorescence spectroscopy techniques and time-dependent density functional theory (TD-DFT) calculations. This work afforded a new method to achieve intriguing chiral geometry and CT optical properties
via
the subtle design and modification of terpyridine ligands.
The novel terpyridine complexes show chiral helical geometry and intriguing CT optical properties
via
subtle 6,6″ modification, distinctly different from the parent bis(2,2′:6′,2″-terpyridine) complexes.
The C(sp
3
)-N bond is ubiquitous in natural products, pharmaceuticals, biologically active molecules and functional materials. Consequently, the development of practical and efficient methods for ...C(sp
3
)-N bond formation has attracted more and more attention. Compared to the conventional ionic pathway-based thermal methods, photochemical processes that proceed through radical mechanisms by merging photoredox and transition-metal catalyses have emerged as powerful and alternative tools for C(sp
3
)-N bond formation. In this review, recent advances in the burgeoning field of C(sp
3
)-N bond formation
via
metallaphotoredox catalysis have been highlighted. The contents of this review are categorized according to the transition metals used (copper, nickel, cobalt, palladium, and iron) together with photocatalysis. Emphasis is placed on methodology achievements and mechanistic insight, aiming to inspire chemists to invent more efficient radical-involved C(sp
3
)-N bond-forming reactions.
In this review, the state-of-the-art advances in radical-involved C(sp
3
)-N bond formation
via
metallaphotoredox catalysis have been highlighted, which are organized according to different catalytic modes, reaction types, and substrate classes.
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•Thermodynamics of the NSMR in the presence of CaF2 was firstly analyzed.•Concentrating Ni with CaF2 addition under different factors was further studied.•Transformation mechanism of ...minerals during the NSMR process was investigated.•Reaction kinetics was firstly examined, and Ea = 309.16 kJ mol−1 was determined.
Laterite ore is the most important primary base source of nickel, however low-nickel saprolitic laterite is difficult to economically utilize. This study aims to investigate the proposed nonmolten-state metalized reduction (NSMR) technology for saprolitic laterite. First, the thermodynamics of NSMR in the presence of calcium fluoride was analyzed using laterite from Southwest China as raw material. Then, the process for concentrating nickel and iron under different factors was systematically studied. Subsequently, the behavior of nickel and iron during the NSMR process was analyzed. Lastly, the kinetics of the metalized reduction process was examined, and the reaction apparent activation energy was determined. Results showed that nickel and iron recoveries can reach as high as 92.9% and 84.6%, respectively, and these two metals are produced in the form of nickel–iron concentrate, which can be used as raw material for steel making. Calcium fluoride can inhibit nickel from entering the nickel-bearing magnesium silicate phase, avoiding the inertness of nickel and considerably increasing its metallization. The reaction process of NSMR conforms to the Avrami–Eroféev reaction model (n = 0.5) and the apparent activation energy (Ea) is 309.16 kJ mol−1. This research demonstrates the theoretical perfection of the proposed NSMR technology, which may realize the commercial utilization of worldwide low-nickel ore in a long-term stagnant state.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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